Background: Honeybee’s venom is potent anticancer drug without exhibiting any side effects. Skin Basal Cell Carcinoma (SBCC) is a common malignancy. It can cause significant local destructions depending on affected site. The diagnosis of SBCC can be suspected from clinical findings and confirmation of diagnosis histopathology. The present SBCC is recurrent and aggressive in the skin of head [upper right, in front of the right ear]; the patient was 65 years old in time of first intervention.

Materials & Methods: Following the lesions primarily surgically excised, the malignant growths recurrent and visual recognition occurred after 1 year from first operation, then another (the second) surgical removal of SBCC from affected skin with removal of all skin layers near the affected site but another recurrence visually occurs after about 4 months, in the form of malignant growth in the skin of right ear. Dry honeybee’s venom 1 mg was dissolved in 1 ml dist. water as injectable solution.  Moreover, ointment contains 2% bee venom was prepared to be used topically inside affected ear as injection is not possible.

Results: Before this novel intervention, the desperate patient situation seems very dangerous; as the new growths appear as continuous spread near the removed skin, so that patient’s family decided to apply more noninvasive and non-surgical intervention. The only precaution was testing the patients to assure she is not hypersensitive to honeybees’ venom. The treatment performed by subcutaneous injection of 0.3 ml from prepared Honeybees venom (0.1 % conc.) in the skin of affected part of the ear. Subcutaneous infiltration was applied around the lesions of about 0.5 ml as well, topical application of the ointment inside inner part of affected ear. This process repeated daily with cleaning of the ear every time by suitable safe and sterile saline solutions. Management of healing process was enhanced by ascorbic acid solution as topical application on dead cancer cells and to help in exudates debris removal. The complete removal of malignant growths and recovery obtained after 1 month from first bee venom injections. No recurrence of SBCC seen for 3 yrs. 

Conclusions: Honeybees venom is highly effective and safe anticancer drug that can be used for all patients’ categories of all ages. Regarding the present case invasive surgical intervention was not the good choice from the beginnings, as recurrence and giving chance for spreading following the time lapse between every surgery.

Basal cell carcinoma (BCC), first described by Jacob in 1827 [1]. It is the most common malignant neoplasm of humans. SBCC is highly destructive malignant tumor that spread by invasion to adjacent areas, primarily affecting the skin layers then attacks other tissues (e.g. cartilages, blood vessels). The identification of high risk SBCC types is based on tumor primary origin, invasiveness characteristics and patient clinical factors include demographic information age (old/childhood), immune suppression, organ transplant, prior burn or radiotherapy, and whether this is a primary or recurrent tumor. Tumor-related features include tumor size and location. High risk includes head and neck skin; deeper invasion beyond reticular dermis, ears and neural and lympho-vascular involvement. On rare occasions, a lesion manifests tenderness or pain which can be a clue to perineural infiltration in the aggressive growth varieties. Sensorimotor compromise has been reported particularly in lesions of the pre-auricular and cheek areas [2]. The typical SBCC aggressive growth tumors tend to show more frequent ulceration and large, untended neoplasms can be locally destructive of eyes, ears and nares [3].

The venom of the honeybees’ worker causes certain pain at the site of the sting, moderate swelling and slight reddening. In the act of stinging, the venom sac and attached muscles are torn from the bee, causing its death. The muscles then continue to work the sting deeper into the wound and inject further venom. To prevent this, the sting should be scraped out with a fingernail (not grasped and pulled out, as these forces all remaining venom into the wound) [4]. Some people develop acute allergic reactions to bee stings. An allergic reaction becomes evident in less than an hour and consists of extreme difficulty in breathing, heart irregularity, shock, splotched skin, and speech difficulty. A person showing signs of an allergic reaction should see a medical doctor immediately [5-6]. Bee venom once excreted from bee’s stings is a clear liquid, turns to forms whitish crystals when exposed to air. Bee venom is a mixture of histamine, pheromones, enzymes, peptides, amino acids and other acids, with over 100 components in total. The main enzymes present are phospholipase A, hyaluronidase, and lecithinase; while the main peptides are mellitin, apamin and peptide 401 (a powerful anti-inflammatory agent). Mellitin, a cationic peptide of 26 amino acid length, makes up 50% of the dry weight of bee venom, and acts as anticoagulants. It also lowers blood pressure, causes histamine release. Both mellitin and apamin cause the body to release cortisol, a natural steroid, while peptide 401 is a powerful anti-inflammatory agent. The main amino acids in bee venom are cysteine and methionine, both of which contain sulphur. Sulphur is important in inducing cortisol release from the adrenal glands. Histamine makes up 0.9% of venom, and causes itching and pain at the site of the sting. The acids present, which include formic, hydrochloric and orthophosphoric acids, are now believed to be much less important in causing pain than was previously thought. Honeybee Venom (HBV) has been recognized as anti-cancer drug in vitro and in vivo (stings of honeybees on the affected area or the extracted bee venom by intramuscular injection). The venom stimulates the release of cortisol, and so is effective in the treatment of rheumatic disorders such as Multiple Sclerosis, rheumatoid arthritis and gout. Mellitin is believed to be the main active agent. Bee venom therapy is one aspect of apitherapy (use of bee products for curing disease). Mellitin is also being investigated as an anti-cancer agent. By modifying the mellitin molecule to prevent allergic reaction, and attaching a cancer-specific antibody (this combination of toxin and antibody is called an immunotoxin), researchers hope to produce a ‘magic bullet’ treatment - so called because it would only destroy cancer cells (unlike conventional chemotherapy agents, which destroy all types of cell, causing unpleasant side effects such as vomiting and hair loss) [6-29].

Following the lesions primarily surgically excised, the malignant growths recurrent and visual recognition occurred after 1 year from first operation, then another (the second) surgical removal of SBCC from affected skin with removal of all skin layers near the affected site but another recurrence visually occurs after about 4 months, in the form of malignant growth in the skin of right ear. Dry honeybee’s venom 1 mg was dissolved in 1 ml dist. water as injectable solution.  Moreover, ointment contains 2

Honeybee’s venom is potent anticancer drug without exhibiting any side effects. Skin Basal Cell Carcinoma (SBCC) is a common malignancy. SBCC has almost no reports of tendency for metastasis. It can cause significant local destructions depending on affected site. The diagnosis of SBCC can be suspected from clinical findings and confirmation of diagnosis histopathology. The present SBCC is recurrent and aggressive in the skin of head [upper right, in front of the right ear]; the patient was 65 years old in time of first intervention.

Following the lesions primarily surgically excised, the malignant growths recurrent and visual recognition occurred after 1 year from first operation, then another (the second) surgical removal of SBCC from affected skin with removal of all skin layers near the affected site but another recurrence visually occurs after about 4 months, in the form of malignant growth in the skin of right ear. Dry honeybee’s venom 1 mg was dissolved in 1 ml dist. water as injectable solution.  Moreover, ointment contains 2

Skin Basal Cell Carcinoma (SBCC) is a common malignancy affecting most probably populations with light skin. SBCC can cause significant local destructions depending on affected site. Biological transformation of BCC tends to occur at the base and edges of the growing neoplasm. The diagnosis of BCC can be suspected from clinical findings and confirmation of diagnosis requires histopathology of biopsy [1-3].

Malignant tumor of basal cell carcinoma of hairy skin of the head and the ear, the anticancer effects of Apis mellifera L’s venom (Honeybees) drug as injectable solutions (0.1% the safe dose), have the potency to treat these conditions and preventing the spread of cancer. Bee venom is potent drug, with zero side effects in cases not hypersensitive against it. It cures the affected skin in very short time, without disfiguration of the patient body parts. Surgery was wrong choice in this case, giving more time for tumor cells to spread to the adjacent areas, leaving patients suffering another surgical intervention with permanent disfiguration of skin.Very small percentages of human have showed skin allergy from bee venom. However, Bee venom is safe drug when used in the recommended doses. Doses of bee venom which consider safe depends upon age, health conditions, type of illness, degree of affections, severity of illness, however in malignancy it is of special regime for every single case, depending on the practitioner experience and knowledge which should be of higher level [15-29].

Bee venom [Apis mellifera L] is safe and effective anticancer drug. As described by: Cassier et al., (1994) study the contribution of the sting sheaths of the worker to the defensive behavior of a bee colony. The structure of the proximal part of the sting sheath integument has all the characteristics of a primitive exocrine gland: porous cuticle with enlarged pore canals and epicuticular pores, and hypertrophied epithelial cells secreting an electron dense material. The non-volatile part of the secretory product embedded the setae of the sheaths. Individual recipient guards in the laboratory and as a group at hive entrances in a bee yard displayed defense behavior only when stimulated with either sting sheaths or with setaceous membrane, but not with any other gland or organ. Enhanced defensive reaction of guards has been observed when a venom gland or Koschewnikow's glands are added to either sting sheaths or to setaceous membrane. We demonstrate for the first time that the sting sheaths have the structure of an exocrine gland and that their secretions induce defensive behavior in guards [4].In agreement with: Moreau, (2012) who mentioned that many hymenopteran species, whatever their life style, have also evolved venom with properties which enable it to regulate microbial infections. Stinging Hymenoptera seems to constitute an under-exploited ecological niche for agents of vector-borne disease. Few parasitic or mutualistic microorganisms have been reported to be hosted by venom-producing organs or to be transmitted to stung animals. This may result from the presence of potent antimicrobial molecules in venoms, histological features of venom apparatuses and selective effects of venoms on immune defenses of targeted organisms [5].In accordance with: Islam et al., (2017) have mentioned that Melittin (MEL), a major peptide component of bee venom, is an attractive candidate for cancer therapy. This agent has shown a variety of anti-cancer effects in preclinical cell culture and animal model systems [6].

In accordance with: Xinjing Wang et al., (2017) have investigated the anti-cancer activity of melittin and its regulated mechanism(s) in the PDAC models. Melittin was found to suppress tumor growth by promoting cell apoptosis and cell-cycle arrest. Their study has indicated that melittin is capable of suppressing tumor growth and promoting gemcitabine sensitivity in PDAC by down regulating cholesterol pathway [7]. In accordance with: Miran Jo et al., (2011)have investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. They results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway [8]. In accordance with: Jeong-Eun Huh et al., (2009)havementioned that honeybees’s venom significantly inhibited the viability of Lewis lung carcinoma (LLC) cells but did not affect peripheral blood mononuclear lymphocytes (PBML) cells. BV also inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). The western blotting analysis showed that BV inhibited AKT and MAPK phosphorylation in LLC cells and HUVECs and down regulated expression of VEGF and VEGFR-2 of LLC cells and HUVECs. They discover that Bee Venom effectively disrupted VEGF-induced neovascularization in Matrigel plugs in their in vivo angiogenesis assay. When given subcutaneously, Bee Venom was significantly suppressed tumor angiogenesis through inhibition of VEGF and VEGFR-2 in LLC model. Mice bearing subcutaneous LLC tumors were treated with 1 μg/ml or 10 μg/ml of Bee Venom, showing reductions ranging between 49% and 62% in primary tumor volume and reduction of spontaneous pulmonary metastasis occurrences. Furthermore, BV treatment in the spontaneous lung metastases model after primary tumor excision prolonged their median survival time from 27 to 58 days. These results suggest that the tumor-specific anti-angiogenic activity of Bee Venom takes effect during different stages of tumor progression by blocking the tyrosine phosphorylation of VEGFR-2, and validate the application of BV in lung cancer treatment [9]. In accordance with: Son et al., (2007)have mentioned BV contains a variety of peptides, including melittin, apamin, adolapin, the mast-cell-degranulating (MCD) peptide, enzymes (i.e., phospholipase [PL] A (2), biologically active amines (i.e., histamine and epinephrine), and non-peptide components which have a variety of pharmaceutical properties [10]. In accordance with: Oršolić, (2012) who mentioned that honeybee’s venom has been used in the treatment of some immune-related diseases, as well as in treatment of tumors. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects [11].

However, the antimicrobial effects of bee venom are overwhelming. Socarras et al., (2017) havementioned that Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known forms of B. burgdorferi. In this study, natural antimicrobial agents such as Apis mellifera venom and a known component, melittin, were tested using SYBR Green I/PI, direct cell counting, biofilm assays combined with LIVE/DEAD and atomic force microscopy methods. The obtained results were compared to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone, Daptomycin, which were recently found to be effective against Borrelia persisters. Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form. These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use [12]. In accordance with: Park et al., (2011)have mentioned that Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells (in vitro study). These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death (in vivo study). Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death [13].

In accordance with: Zheng et al., (2015) have mentioned that Bee venom (BV) has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. They found that BV inhibited growth of colon cancer cells through induction of apoptosis, also found that the expression of death receptor (DR) 4, DR5, p53, p21, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was increased by BV treatment in a dose dependent manner (0-5 μg/ml). Consistent with cancer cell growth inhibition, the DNA binding activity of nuclear factor kappa B (NF-κB) was also inhibited by BV treatment. Besides, they found that BV blocked NF-κB activation by directly binding to NF-κB p50 subunit. Moreover, combination treatment with BV and p50 siRNA or NF-κB inhibitor augmented BV-induced cell growth inhibition. However, p50 mutant plasmid (C62S) transfection partially abolished BV-induced cell growth inhibition. BV significantly suppressed tumor growth in vivo. Therefore, these results suggested that BV could inhibit colon cancer cell growth, and these anti-proliferative effects may be related to the induction of apoptosis by activation of DR4 and DR5 and inhibition of NF-κB [14]. 

Honeybees venom is highly effective and safe anticancer drug that can be used for all patients’ categories of all ages. Regarding the present case invasive surgical intervention was not the good choice from the beginnings, as recurrence and spreading follows. The patient and her family seek bee venom treatment after failure of multiple surgery and recurrence attacking vital organs (the ear). Fearing from spread to the brain, and destroying the ear, with life threatening conditions, they agree and seek this treatment. The rapid response and the healing effects of bee venom have certain positive psychological effects on family and the patient, after they were very sorry and worried about the progress and spread of cancer, they became more hopeful and happy after only few days from treatment by bee venom. This novel method has been protecting the patient from the severe painful surgical intervention. It is more effective, safe and more successful in removing BCC.